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1.
Acta Bioeng Biomech ; 26(1): 99-107, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-39219075

ABSTRACT

Purpose: The aim of this study was to measure blood and blood mimicking fluids viscosity at different shear rates (on the interval of 0.1-5000 1/s and 0.1-10000 1/s) while taking into consideration the measuring device's capability and blood's characteristics. We also provided the measurement results of the most accurate measuring program. Methods: We measured blood samples from five donors, and four different blood mimicking fluid compositions. The measurements were done on an Anton Paar Physica MCR301 rotational rheometer with two measuring programs varying in the shear rate intervals, the number of measuring points and the measuring point durations. Results: The results confirmed the significant shear thinning and thixotropic effects of blood. Blood mimicking fluids also had these characteristics. The measured blood viscosity values are in agreement with those of the literature. Conclusions: It can be concluded that the step test program was able to give more stable results as the measured torque was over the nominal limit of 0.05 ìNm over 0.1 1/s and over the selected torque limit of 0.5 ìNm over 31.6 1/s. Blood mimicking fluid measurement results were different from that of the literature due to different measuring conditions. The sample consisting of water, glycerol and starch mimicked well blood's behaviour and viscosity values at 37 degrees Celsius.


Subject(s)
Blood Viscosity , Humans , Shear Strength , Stress, Mechanical , Viscosity
2.
Eur J Pharm Biopharm ; 203: 114455, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39147171

ABSTRACT

The transport of drug/magnetic particle (MP) conjugates in the presence of a Magnetic Field (MF) in Drug Eluting Stents (DESs) is modeled numerically using the Finite Volume Method (FVM). The effects of physiological conditions corresponding to different degrees of calcification, drug particles sizes and hematocrit level, were analyzed by investigating the roles of the tissue permeability, its anisotropy and the plasma viscosity. It was found that both in the absence and presence of the MF, as the tissue permeability decreases or the plasma viscosity increases, the free-phase drug and Extracellular Matrix (ECM)-bound phase contents increase. Stronger tissue anisotropy leads to a decrease of the free-phase drug content and an increase of the ECM-bound phase content. Within the explored ranges, the Specific Receptor (SR)-bound phase of the drug was found to be insensitive to the tissue permeability and plasma viscosity, and to be larger in anisotropic tissues. The activation of the MF leads systematically to larger free-phase drug contents, with the increases most prominent at smaller tissue permeability, anisotropy and plasma viscosity. On the other hand, the effects on the ECM-bound phase content are found to be stronger at larger permeability, smaller plasma viscosity and lower tissue anisotropy. For an isotropic tissue, the MF induces a decrease of the ECM-bound phase content at early times, followed by an increase at later times. For the considered ranges of permeability and viscosity, the MF does not seem to have any noticeable effects on the SR-bound phase. However, this phase of the drug tends to increase with the activation of the MF in isotropic tissues and is unchanged in anisotropic ones. These reported effects of the MF hold promise for alleviating two factors contributing to In-Stent Restenosis, namely the polymer coating width and thickness. The study reveals that a narrower or thinner polymer layer, in combination with the MF, can mimic the drug release dynamics of a wider or thicker polymer layer in the absence of the MF. The corresponding width and thickness of the magnetized stents, that we referred to as the equivalent polymer width (EPW) and equivalent polymer thickness (EPT) were determined and their dependence on the tissue permeability, isotropy and the plasma viscosity, was investigated. The study shows that it is possible to achieve the same drug delivery with polymer coating of half the width or half the thickness of the non-magnetized stent when an electric intensity of 3A is used.


Subject(s)
Drug-Eluting Stents , Magnetic Fields , Polymers , Polymers/chemistry , Humans , Permeability , Anisotropy , Particle Size , Drug Delivery Systems/methods , Blood Viscosity
3.
Proc Natl Acad Sci U S A ; 121(33): e2323016121, 2024 Aug 13.
Article in English | MEDLINE | ID: mdl-39088388

ABSTRACT

Blood plasma viscosity (PV) is an established biomarker for numerous diseases. Measurement of the shear PV using conventional rheological techniques is, however, time consuming and requires significant plasma volumes. Here, we show that Brillouin light scattering (BLS) and angle-resolved spectroscopy measurements of the longitudinal PV from microliter-sized plasma volumes can serve as a proxy for the shear PV measured using conventional viscometers. This is not trivial given the distinct frequency regime probed and the longitudinal viscosity, a combination of the shear and bulk viscosity, representing a unique material property on account of the latter. We demonstrate this for plasma from healthy persons and patients suffering from different severities of COVID-19 (CoV), which has been associated with an increased shear PV. We further show that the additional information contained in the BLS-measured effective longitudinal PV and its temperature scaling can provide unique insight into the chemical constituents and physical properties of plasma that can be of diagnostic value. In particular, we find that changes in the effective longitudinal viscosity are consistent with an increased suspension concentration in CoV patient samples at elevated temperatures that is correlated with disease severity and progression. This is supported by results from rapid BLS spatial-mapping, angle-resolved BLS measurements, changes in the elastic scattering, and anomalies in the temperature scaling of the shear viscosity. Finally, we introduce a compact BLS probe to rapidly perform measurements in plastic transport tubes. Our results open a broad avenue for PV diagnostics based on the high-frequency effective longitudinal PV and show that BLS can provide a means for its implementation.


Subject(s)
Blood Viscosity , COVID-19 , Humans , Blood Viscosity/physiology , COVID-19/blood , COVID-19/diagnosis , SARS-CoV-2 , Scattering, Radiation , Plasma/chemistry , Light , Rheology/methods , Male
4.
Soft Matter ; 20(33): 6681-6683, 2024 Aug 22.
Article in English | MEDLINE | ID: mdl-39087430

ABSTRACT

In this answer, we provide our arguments in support of the possibility to observe the single file-organization of red blood cells in microvessels and the resulting unexpectedly weak increase of blood viscosity with increasing hematocrit, the physiological relevance of which was questioned in the comment. The key element is that the equivalent diameter in 3D for the maximal hematocrit corresponding to a single file of red blood cells is about 10 µm and not 20 µm, as in 2D. In addition, the viscosity contrast (ratio between the cell internal and external viscosities) value must be chosen in our 2D simulation in a such a way that the effective viscosity (a linear combination of the internal, external and membrane viscosities) be close to that of a real RBC. Taking these two facts into account, we find a reasonable agreement between our 2D viscosity simulations data and experimental data, despite the crude 2D assumption.


Subject(s)
Erythrocytes , Rheology , Erythrocytes/cytology , Blood Viscosity , Humans , Viscosity , Hematocrit
6.
J Am Heart Assoc ; 13(15): e034162, 2024 Aug 06.
Article in English | MEDLINE | ID: mdl-39041635

ABSTRACT

BACKGROUND: Elevated blood viscosity (BV), a critical determinant in blood rheology, is a contributing factor in cerebrovascular diseases. The specific influence of BV on small vessel disease burden remains unexplored. This study aims to examine the relationship between BV and regional white matter hyperintensity (WMH) volume in patients with acute ischemic stroke. METHODS AND RESULTS: We enrolled a cohort of 302 patients with acute ischemic stroke or transient ischemic attack who were admitted to a hospital within 7 days of symptom onset in this study. We measured whole BV using a scanning capillary-tube viscometer and categorized systolic blood viscosity into 3 groups based on established references. We quantified and normalized WMH volumes using automated localization and segmentation software by NEUROPHET Inc. We performed multivariable logistic regression analysis to assess the correlation between systolic BV and WMH. The mean subject age was 66.7±13.4 years, and 38.7% (n=117) of the participants were female. Among a total of 302 patients, patients with higher deep WMH volume (T3) were typically older and had an atrial fibrillation, strokes of cardioembolic or undetermined cause, elevated levels of C-reactive protein, diastolic blood viscosity and systolic BV. A multivariable adjustment revealed a significant association between high systolic BV and increased deep-WMH volume (odds ratio [OR], 2.636 [95% CI, 1.225-5.673]). CONCLUSIONS: Elevated systolic BV is more likely to be associated with deep WMH volume in patients with acute ischemic stroke or transient ischemic attack. These findings reveal novel therapeutic strategies focusing on blood rheology to enhance cerebral microcirculation in stroke management.


Subject(s)
Blood Viscosity , Ischemic Stroke , White Matter , Humans , Female , Male , Aged , Ischemic Stroke/blood , Ischemic Stroke/diagnostic imaging , Ischemic Stroke/physiopathology , Middle Aged , White Matter/diagnostic imaging , White Matter/pathology , Magnetic Resonance Imaging , Leukoencephalopathies/blood , Leukoencephalopathies/diagnostic imaging , Leukoencephalopathies/physiopathology , Leukoencephalopathies/etiology , Systole , Risk Factors , Aged, 80 and over , Ischemic Attack, Transient/blood , Ischemic Attack, Transient/physiopathology
7.
Molecules ; 29(13)2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38998977

ABSTRACT

Paeonia lactiflora Pall. (PLP) is thought to promote blood circulation and remove blood stasis. This study used blood component analysis, network pharmacology, and molecular docking to predict the mechanism of PLP in the treatment of blood stasis syndrome (BSS). PLP was processed into Paeoniae Radix Alba (PRA) and Paeoniae Radix Rubra (PRR). PRA and PRR could significantly reduce whole blood viscosity (WBV) at 1/s shear rates and could increase the erythrocyte aggregation index (EAI), plasma viscosity (PV), and erythrocyte sedimentation rate (ESR) of rats with acute blood stasis. They prolonged the prothrombin time (PT), and PRR prolonged the activated partial thromboplastin time (APTT). PRA and PRR increased the thrombin time (TT) and decreased the fibrinogen (FBG) content. All the results were significant (p < 0.05). Ten components of Paeoniflorin, Albiflorin, Paeonin C, and others were identified in the plasma of rats using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). A protein-protein interaction network (PPI) analysis showed that AKT1, EGFR, SRC, MAPK14, NOS3, and KDR were key targets of PLP in the treatment of BSS, and the molecular docking results further verified this. This study indicated that PLP improves BSS in multiple ways and that the potential pharmacological mechanisms may be related to angiogenesis, vasoconstriction and relaxation, coagulation, and the migration and proliferation of vascular cells.


Subject(s)
Molecular Docking Simulation , Network Pharmacology , Paeonia , Paeonia/chemistry , Animals , Rats , Chromatography, High Pressure Liquid/methods , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/chemistry , Male , Blood Viscosity/drug effects , Rats, Sprague-Dawley , Disease Models, Animal
8.
Photodiagnosis Photodyn Ther ; 48: 104264, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38971525

ABSTRACT

PURPOSE: To evaluate the retinal vessel density (VD) with optical coherence tomography angiography (OCTA) in asymptomatic patients affected by Waldenström macroglobulinemia (WM) without hyperviscosity syndrome (HVS) and to highlight the presence of microvascular damage in theese clinically asymptomatic WD patients. DESIGN: Prospective study. METHODS: A total of 43 eyes from 43 WM patients (24 females, 19 males, mean age 55.1 ± 13.6 years) were enrolled from January 2023 to December 2023 in the Eye Clinic of the University of Naples Federico II. Along with WM patients, 40 healthy subjects (HS) (20 females, 20 males, mean age 52.3 ± 15.6 years) with a normal ophthalmic examination and no history of intraocular surgery or retinal pathologic features were included as control group All patients and controls underwent OCTA RESULTS: The two groups were not significantly different for age and sex Visual acuity examination showed no statistically significant difference in BCVA between controls and patients Compared to HS, WD patients showed lower VD values in the SCP in the whole image (47.95 ± 5.17% vs. 52.99 ± 2.52 %; p < 0.001), as well as in the parafovea (53.01 ± 6.69% vs. 55.30 ± 2.61 %; p = 0.002), and fovea (21.38 ± 9.01% vs. 30.31 ± 5.84 %; p < 0.0001). On the other hand, in the DCP VD values were significantly higher in patients compared to controls in the whole image (55.82 ± 8.07% vs. 50.83 ± 5.46 %; p = 0.005), as well as in the parafovea (56.76 ± 6.26% vs. 52.59 ± 5.46 %; p = 0.0001), and fovea (38.75 ± 8.59% vs. 33.43 ± 8.68 %; p < 0.0001). CONCLUSION: The finding that OCTA confirmed the presence of widespread microvascular damage in WD patients clinically silent. Thus, OCTA is a safe rapid imaging technique that could represent a valid biomarker of systemic vascular dysfunction.


Subject(s)
Tomography, Optical Coherence , Waldenstrom Macroglobulinemia , Humans , Male , Female , Waldenstrom Macroglobulinemia/diagnostic imaging , Middle Aged , Pilot Projects , Prospective Studies , Tomography, Optical Coherence/methods , Retinal Vessels/diagnostic imaging , Blood Viscosity , Aged , Fluorescein Angiography/methods , Adult , Case-Control Studies , Visual Acuity
9.
Lab Chip ; 24(13): 3305-3314, 2024 06 25.
Article in English | MEDLINE | ID: mdl-38869225

ABSTRACT

Physical properties of blood plasma, such as viscosity, serve as crucial indicators of disease. The inherent capillary effect of paper microchannels, coupled with minimal sample requirement, stimulated the advancement of paper-based viscometers. This study presents a precise, non-contact optoelectronic system using a microfluidic platform for the measurement of blood plasma viscosity. Microchannels were defined onto the filter paper using an available and inexpensive wax crayon, without the need for conventional wax printing equipment. The time required for the 5 µL sample to pass a specific distance was measured using two pairs of infrared sensors. Subsequently, this data was sent to the microcontroller, which automatically calculated the viscosity. Throughout the measurements, sample temperature was maintained at a constant 37 °C through an integrated heater with automated control. The microfluidic platform successfully processed real samples, yielding viscosity measurements in under three minutes. Evaluation with fetal bovine serum, spiked with varying protein concentrations in both native and denatured states, demonstrated a precision exceeding 96% compared to conventional Ostwald viscometer readings. For human subjects exhibiting pathologies affecting serum and plasma viscosity compared to physiological norms, strong correlations were observed between resultant values and clinical diagnoses. The proposed device aims to replace expensive and complex optical equipment, offering a safer alternative for measuring plasma viscosity. Unlike similar devices, it eliminates the risk of component deformation due to chemical contact or unsafe irradiation.


Subject(s)
Blood Viscosity , Lab-On-A-Chip Devices , Humans , Microfluidic Analytical Techniques/instrumentation , Cattle , Animals , Point-of-Care Systems , Equipment Design
10.
Biomech Model Mechanobiol ; 23(5): 1765-1780, 2024 Oct.
Article in English | MEDLINE | ID: mdl-38884891

ABSTRACT

Neurological complexities resulting from surgery requiring cardiopulmonary bypass (CPB) remain a major concern, encompassing a spectrum of complications including thromboembolic stroke and various cognitive impairments. Surgical manipulation during CPB is considered the primary cause of these neurological complications. This study addresses the overall lack of knowledge concerning CPB hemodynamics within the aorta, employing a combined experimental-computational modeling approach, featuring computational fluid dynamics simulations validated with an in vitro CPB flow loop under steady conditions. Parametric studies were systematically performed, varying parameters associated with CPB techniques (pump flow rate and hemodiluted blood viscosity) and properties related to formed emboli (size and density). This represents the first comprehensive investigation into the individual and combined effects of these factors. Our findings reveal critical insights into the operating conditions of CPB, indicating a positive correlation between pump flow rate and emboli transport into the aortic branches, potentially increasing the risk of stroke. It was also found that larger emboli were more often transported into the aortic branches at higher pump flow rates, while smaller emboli preferred lower flow rates. Further, as blood is commonly diluted during CPB to decrease its viscosity, more emboli were found to enter the aortic branches with greater hemodilution. The combined effects of these parameters are captured using the non-dimensional Stokes number, which was found to positively correlate with emboli transport into the aortic branches. These findings contribute to our understanding of embolic stroke risk factors during CPB and shed light on the complex interplay between CPB parameters.


Subject(s)
Aorta , Cardiopulmonary Bypass , Embolism , Humans , Embolism/physiopathology , Aorta/physiopathology , Aorta/surgery , Models, Cardiovascular , Computer Simulation , Hemodynamics , Blood Viscosity , Hydrodynamics
11.
Noise Health ; 26(121): 148-152, 2024.
Article in English | MEDLINE | ID: mdl-38904815

ABSTRACT

OBJECTIVE: The increase in patient flow, replacement of medical equipment, and variations in surrounding environments induce increasingly serious acoustic environment problems in hospitals. This study aims to provide additional bases for the formulation of subsequent management plans in clinical practice by analyzing the influence of the acoustic environment in wards and the postoperative rehabilitation effect among patients with oral cancer. METHODS: The medical records of 210 patients with oral cancer undergoing surgical treatment in Jinan Stomatological Hospital from February 2020 to October 2022 were selected for retrospective analysis. Patients with the acoustic environment in wards >55 and ≤55 dB were classified as groups A and B, respectively, according to the acoustic environment in wards. The effects of the acoustic environment in wards on postoperative blood pressure, blood viscosity, and blood glucose fluctuation (BGF) were observed to further analyze their relationship. RESULTS: No significant difference was observed in indices such as preoperative systolic pressure (SP), diastolic pressure (DP), cardiac output (CO), postoperative CO, total cholesterol, and low- and high-density lipoproteins between the two groups (P > 0.05). The SP, DP, whole blood low-shear viscosity (WBLSV), whole blood middle-shear viscosity (WBMSV), whole blood high-shear viscosity (WBHSV), and BGF in group B were significantly lower than group A (P < 0.05). Correlation results showed that the total mean value of the acoustic environment in wards was positively correlated with SP, DP, WBLSV, WBMSV, WBHSV, and BGF (P < 0.05). CONCLUSION: The high acoustic environment in wards is significantly positively correlated with postoperative blood pressure, blood viscosity, and BGF in patients with oral cancer. The hospital should focus on and strengthen the management of the acoustic environment in wards, providing additional schemes to promote the postoperative recovery of patients with oral cancer.


Subject(s)
Blood Pressure , Mouth Neoplasms , Humans , Retrospective Studies , Male , Female , Mouth Neoplasms/surgery , Mouth Neoplasms/rehabilitation , Middle Aged , Adult , Blood Viscosity , Aged , Blood Glucose , Noise
12.
ACS Appl Bio Mater ; 7(7): 4710-4724, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38920024

ABSTRACT

ß-Thalassemia especially transfusion-dependent thalassemia (TDT) associates with a hypercoagulable state, which is the main cause of thromboembolic events (TEE). Plasma viscosity and rheological parameters could be essential markers for determining hypercoagulable state in ß-thalassemia patients. The traditional methods for measuring viscosity are often limited by large sample volumes and are impractical for routine clinical monitoring. The compact differential dynamic microscopy-based device (cDDM), an optical microscopy for quantitative rheological assessment, was developed and applied for prognosis of the hypercoagulable state in ß-TDT with and without splenectomy. The device was performed plasma viscosity measurement using low plasma volume (8 µL) and revealed a value as modulus of complex viscosity |η(ω)| in 7 min. We also parallelly demonstrated the correlation of the viscosity and related-coagulable parameters: complete blood count, prothrombin time (PT), activated partial thromboplastin time (APTT), protein C (PC), protein S (PS), CD62P and CD63 expression, and platelet aggregation test. The thalassemia plasma exhibited a higher value of |η(ω)| than healthy plasma, which can represent a different viscoelastic property among the groups. Even all related-coagulable parameters indicated hypercoagulable state in both nonsplenectomies and splenectomies ß-TDT patients when compared to control, only high platelet numbers significantly correlated to high plasma viscosity in the splenectomy group. However, the other coagulable parameters have shown a trend of positive relationship with high plasma viscosity in all ß-1thalassemia TDT patients. The relative results suggested that our device would be an approach tool for early detection of hypercoagulable state in transfusion-dependent-ß-thalassemia patients, which can help to prevent TEE and the critical consequent-complications.


Subject(s)
Materials Testing , Thrombophilia , beta-Thalassemia , Humans , beta-Thalassemia/blood , beta-Thalassemia/complications , Thrombophilia/blood , Thrombophilia/diagnosis , Blood Transfusion , Microscopy , Biocompatible Materials/chemistry , Blood Viscosity , Male , Particle Size , Early Diagnosis , Female
13.
J Appl Physiol (1985) ; 137(3): 494-509, 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-38813609

ABSTRACT

In humans and many animals, a trade-off between a sufficiently high concentration of erythrocytes (hematocrit) to bind oxygen and sufficiently low blood viscosity to allow rapid blood flow has been achieved during evolution. The optimal value lies between the extreme cases of pure blood plasma, which cannot practically transport any oxygen, and 100% hematocrit, which would imply very slow blood flow or none at all. As oxygen delivery to tissues is the main task of the cardiovascular system, it is reasonable to expect that maximum oxygen delivery has been achieved during evolution. Optimal hematocrit theory, based on this optimality principle, has been successful in predicting hematocrit values of about 0.3-0.5, which are indeed observed in the systemic circulation of humans and many animal species. Similarly, the theory can explain why a hematocrit higher than normal, ranging from 0.5 to 0.7, can promote better exertional performance. Here, we present a review of theoretical approaches to the calculation of the optimal hematocrit value under different conditions and discuss them in a broad physiological context. Several physiological and medical implications are outlined, for example, in view of blood doping, temperature adaptation, dehydration, and life at high altitudes.


Subject(s)
Oxygen , Hematocrit/methods , Humans , Animals , Oxygen/blood , Oxygen/metabolism , Blood Viscosity/physiology , Models, Cardiovascular , Erythrocytes/physiology , Erythrocytes/metabolism
14.
Soft Matter ; 20(23): 4561-4566, 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38775063

ABSTRACT

Blood is a highly complex fluid with rheological properties that have a significant impact on various flow phenomena. In particular, it exhibits a non-Newtonian elongational viscosity that is comparable to polymer solutions. In this study, we investigate the effect of three different anticoagulants, namely EDTA (ethylene diamine tetraacetic acid), heparin, and citrate, on the elongational properties of both human and swine blood. We observe a unique two stage thinning process and a strong dependency of the characteristic relaxation time on the chosen anticoagulant, with the longest relaxation time and thus the highest elongational viscosity being found for the case of citrate. Our findings for the latter are consistent with the physiological values obtained from a dripping droplet of human blood without any anticoagulant. Furthermore, our study resolves the discrepancy found in the literature regarding the reported range of characteristic relaxation times, confirming that the elongational viscosity must be taken into account for a full rheological characterization of blood. These results have important implications for understanding blood flow in various physiological, pathological and technological conditions.


Subject(s)
Anticoagulants , Anticoagulants/pharmacology , Anticoagulants/chemistry , Humans , Swine , Animals , Blood Viscosity/drug effects , Edetic Acid/chemistry , Edetic Acid/pharmacology , Heparin/pharmacology , Heparin/chemistry , Viscosity , Citric Acid/chemistry , Blood/drug effects , Rheology
15.
PLoS One ; 19(4): e0294095, 2024.
Article in English | MEDLINE | ID: mdl-38669241

ABSTRACT

AIMS: Association between whole blood viscosity (WBV) and an increased risk of cardiovascular disease (CVD) has been reported. However, the causal relationship between WBV and CVD remains not thoroughly investigated. The aim of this study was to investigate the causal relation between WBV and CVD. METHODS: Two-sample Mendelian randomization (MR) was employed, with inverse variance weighting (IVW) as the primary method, to investigate the casual relationship between WBV and CVD. The calculated WBV and medical records of 378,210 individuals participating in the UK Biobank study were divided into halves and analyzed. RESULTS: The means of calculated WBVs were 16.9 (standard deviation: 0.8) and 55.1 (standard deviation: 17.2) for high shear rate (HSR) and low shear rate (LSR), respectively. 37,859 (10.0%) major cardiovascular events (MACE) consisted of 23,894 (6.3%) cases of myocardial infarction (MI), 9,245 (2.4%) cases of ischemic stroke, 10,377 (2.7%) cases of revascularization, and 5,703 (1.5%) cases of coronary heart disease-related death. In the MR analysis, no evidence was found indicating a causal effect of WBV on MACE (IVW p-value for HSR = 0.81, IVW p-value for LSR = 0.47), MI (0.92, 0.83), ischemic stroke (0.52, 0.74), revascularization (0.71, 0.54), and coronary heart disease-related death (0.83, 0.70). The lack of sufficient evidence for causality persisted in other MR methods, including weighted median and MR-egger. CONCLUSIONS: The Mendelian randomization analysis conducted in this study does not support a causal relationship between calculated WBV and CVD.


Subject(s)
Blood Viscosity , Cardiovascular Diseases , Mendelian Randomization Analysis , Humans , Cardiovascular Diseases/genetics , Cardiovascular Diseases/blood , Cardiovascular Diseases/etiology , Female , Male , Middle Aged , United Kingdom/epidemiology , Aged , Risk Factors
16.
J Trace Elem Med Biol ; 84: 127450, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38643593

ABSTRACT

Diabetes mellitus (DM) is a complex, chronic metabolic disorder characterized by impaired regulation of blood glucose levels. Zinc (Zn) is an essential trace elements that plays a role in various physiological processes within the body, including those related to diabetes. The current study was investigated the effect of Zn supplementation on hemorheological parameters in a rat model of DM. After induction of DM, 32 male Wistar albino rats were divided into four groups: control, Zn, DM, and Zn+DM. Whole blood viscosity (WBV) was determined by using digital cone and plate viscometer and plasma viscosity (PV) was determined by a Coulter Harkness capillary viscometer. The rats in the DM Group showed a decrease in both Zn levels and body weight, as well as an increase in glucose levels when compared to the control group. Diabetic rats supplemented with Zn displayed lower blood glucose levels and higher concentrations of Zn compared to the DM Group. The higher PV and lower hematocrit level were measured in DM Group than control group and lower PV, higher hematocrit level were measured in Zn+DM group than DM Group. The WBV was measured at four different shear rates (57.6-115.2 - 172.8-230.4 s -1). A statistically significant increase was observed in the DM group compared to the control group. Additionally, a statistically significant decrease was observed in the Zn+DM Group compared to the DM Group at a shear rate of 230.4 s-1. Erythrocyte rigidity index (Tk) and oxygen delivery index (ODI) were computed under conditions of high shear rate. The rats in the DM group exhibited a reduction in ODI and an elevation in Tk in comparison to the control group. Conversely, the diabetic rats supplemented with Zn exhibited decreased Tk and increased ODI compared to the DM Group. Zn supplementation seems to have a potential beneficial effect for protecting adverse affect of diabetes on hemorheogical parameters and for maintaining vascular health.


Subject(s)
Diabetes Mellitus, Experimental , Hemorheology , Rats, Wistar , Zinc , Animals , Zinc/blood , Zinc/pharmacology , Male , Diabetes Mellitus, Experimental/blood , Diabetes Mellitus, Experimental/drug therapy , Rats , Hemorheology/drug effects , Blood Glucose/metabolism , Blood Viscosity/drug effects , Disease Models, Animal , Body Weight/drug effects , Dietary Supplements
17.
Atherosclerosis ; 392: 117529, 2024 May.
Article in English | MEDLINE | ID: mdl-38583289

ABSTRACT

BACKGROUND: Mechanistic studies suggest that proprotein convertase subtilisin/kexin type 9 inhibitors can modulate inflammation. METHODS: Double-blind, placebo-controlled trial randomized 41 ASCVD subjects with type 2 diabetes with microalbuminuria and LDL-C level >70 mg/dL on maximum tolerated statin therapy received subcutaneous evolocumab 420 mg every 4 weeks or matching placebo. The primary outcomes were change in circulating immune cell transcriptional response, lipoproteins and blood viscosity at 2 weeks and 12 weeks. Safety was assessed in all subjects who received at least one dose of assigned treatment and analyses were conducted in the intention-to-treat population. RESULTS: All 41 randomized subjects completed the 2-week visit. Six subjects did not receive study medication consistently after the 2-week visit due to COVID-19 pandemic suspension of research activities. The groups were well-matched with respect to age, comorbidities, baseline LDL-C, white blood cell counts, and markers of systemic inflammation. Evolocumab reduced LDL-C by -68.8% (p < 0.0001) and -52.8% (p < 0.0001) at 2 and 12 weeks, respectively. There were no differences in blood viscosity at baseline nor at 2 and 12 weeks. RNA-seq was performed on peripheral blood mononuclear cells with and without TLR4 stimulation ("Stress" transcriptomics). "Stress" transcriptomics unmasked immune cell phenotypic differences between evolocumab and placebo groups at 2 and 12 weeks. CONCLUSIONS: This trial is the first to demonstrate that PCSK9 mAB with evolocumab can modulate circulating immune cell properties and highlights the importance of "stress" profiling of circulating immune cells that more clearly define immune contributions to ASCVD.


Subject(s)
Antibodies, Monoclonal, Humanized , Cholesterol, LDL , Monocytes , PCSK9 Inhibitors , Proprotein Convertase 9 , Humans , Antibodies, Monoclonal, Humanized/therapeutic use , Male , Female , Middle Aged , Double-Blind Method , Monocytes/drug effects , Monocytes/metabolism , Monocytes/immunology , Aged , Cholesterol, LDL/blood , Proprotein Convertase 9/metabolism , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/immunology , Anticholesteremic Agents/therapeutic use , Lipoproteins/blood , Treatment Outcome , COVID-19/blood , COVID-19/immunology , Blood Viscosity/drug effects
18.
Am J Hematol ; 99(6): 1103-1107, 2024 06.
Article in English | MEDLINE | ID: mdl-38572662

ABSTRACT

Hyperleukocytosis is an emergency of acute leukemia leading to blood hyperviscosity, potentially resulting in life-threatening microvascular obstruction, or leukostasis. Due to the high number of red cells in the circulation, hematocrit/hemoglobin levels (Hct/Hgb) are major drivers of blood viscosity, but how Hct/Hgb mediates hyperviscosity in acute leukemia remains unknown. In vivo hemorheological studies are difficult to conduct and interpret due to issues related to visualizing and manipulating the microvasculature. To that end, a multi-vessel microfluidic device recapitulating the size-scale and geometry of the microvasculature was designed to investigate how Hct/Hgb interacts with acute leukemia to induce "in vitro" leukostasis. Using patient samples and cell lines, the degree of leukostasis was different among leukemia immunophenotypes with respect to white blood cell (WBC) count and Hct/Hgb. Among lymphoid immunophenotypes, severe anemia is protective against in vitro leukostasis and Hct/Hgb thresholds became apparent above which in vitro leukostasis significantly increased, to a greater extent with B-cell acute lymphoblastic leukemia (ALL) versus T-cell ALL. In vitro leukostasis in acute myeloid leukemia was primarily driven by WBC with little interaction with Hct/Hgb. This sets the stage for prospective clinical studies assessing how red cell transfusion may affect leukostasis risk in immunophenotypically different acute leukemia patients.


Subject(s)
Blood Viscosity , Erythrocyte Transfusion , Humans , Microvessels , Leukostasis/etiology , Hematocrit , Leukemia, Myeloid, Acute/therapy , Leukemia, Myeloid, Acute/blood , Female , Male , Hemoglobins/analysis
19.
Am J Hematol ; 99(7): 1407-1410, 2024 07.
Article in English | MEDLINE | ID: mdl-38622808

ABSTRACT

We investigated highlanders, permanently living at an altitude of 5100 m and compared Chronic Mountain Sickness (CMS) patients with control volunteers. While we found differences in systemic parameters such as blood oxygen content, hematocrit, hemoglobin concentration, and blood viscosity, the mechanical and rheological properties of single red blood cells did not differ between the two investigated groups.


Subject(s)
Altitude Sickness , Erythrocytes , Humans , Altitude Sickness/blood , Male , Adult , Chronic Disease , Female , Hematocrit , Middle Aged , Blood Viscosity , Hemoglobins/analysis , Altitude , Erythrocyte Transfusion , Oxygen/blood
20.
Bull Exp Biol Med ; 176(4): 419-422, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38488961

ABSTRACT

We investigated the effect of a decrease in blood viscosity on the mean BP during isovolumic hemodilution and vasodilating activity of the endothelium in normotensive Wistar rats and spontaneously hypertensive rats (SHR). Blood viscosity was reduced by isovolumic hemodilution (replacement of 10% of circulating blood with an equal volume of plasma). Hemodilution caused the same reduction in blood viscosity by 16% in both groups of rats. In Wistar rats, a decrease in blood viscosity did not significantly change in the mean BP; no significant correlations between blood viscosity and mean BP were observed before and after hemodilution. In SHR, a decrease in blood viscosity led to a significant decrease in the mean BP by 18%. Correlations were found between the mean BP and blood viscosity in SHR before (r=0.63; p=0.028) and after (r=0.71; p=0.009) isovolumic hemodilution. In SHR, a decrease in the index of vasodilating activity of the endothelium due to a decrease in the vasodilatory response to intravenous administration of the endothelium-dependent vasodilator acetylcholine was revealed. In SHR, BP passively follows the change, in this case, the decrease in blood viscosity, which attests to impaired BP regulation in response to changes in shear stress on the vascular endothelium caused by the development of endothelial dysfunction in hypertensive animals.


Subject(s)
Arterial Pressure , Hypertension , Rats , Animals , Rats, Inbred SHR , Rats, Wistar , Blood Viscosity , Rats, Inbred WKY , Blood Pressure/physiology , Endothelium, Vascular
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